Chemical Antagonists of Plasminogen Activator Inhibitor-1: Mechanisms of Action and Therapeutic Potential in Vascular Disease

Simone, Tessa M.; Higgins, Stephen P.; Higgins, Craig E.; Lennartz, Michelle R.; Higgins, Paul J.

doi:10.4172/1747-0862.1000125

Cited by 12 publications

(6 citation statements)

References 97 publications

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“…A decrease in pulmonary MMP protein levels usually accompanies increased PAI-1 protein levels, which ultimately leads to increased ECM deposition and chronic fibrosis (35)(36)(37)(38). Because MMP2 and MMP9 share similar substrates, the Lungs from both female and male mouse offspring (6-wk old) from mothers prenatally exposed to e-cig aerosols with or without nicotine were homogenized, and ECM-related protein markers were analyzed by Western blot.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to Electronic-Cigarette Aerosols Leads to Sex-Dependent Pulmonary Extracellular-Matrix Remodeling and Myogenesis in Offspring Mice

Wang

Sundar

Blum

et al. 2020

Am J Respir Cell Mol Biol

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Electronic-cigarette (e-cig) vaping is a serious concern, as many pregnant women who vape consider it safe. However, little is known about the harmful effects of prenatal e-cig exposure on adult offspring, especially on extracellular-matrix (ECM) deposition and myogenesis in the lungs of offspring. We evaluated the biochemical and molecular implications of maternal exposure during pregnancy to e-cig aerosols on the adult offspring of both sexes, with a particular focus on pulmonary ECM remodeling and myogenesis. Pregnant CD-1 mice were exposed to e-cig aerosols with or without nicotine, throughout gestation, and lungs were collected from adult male and female offspring. Compared with the air-exposed control group, female mice exposed to e-cig aerosols, with or without nicotine, demonstrated increased lung protein abundance of LEF-1 (lymphoid enhancer-binding factor 1), fibronectin, and E-cadherin, whereas altered E-cadherin and PPARg (peroxisome proliferator-activated receptor g) levels were observed only in males exposed to e-cig aerosols with nicotine. Moreover, lipogenic and myogenic mRNAs were dysregulated in adult offspring in a sex-dependent manner. PAI-1 (plasminogen activator inhibitor-1), one of the ECM regulators, was significantly increased in females exposed prenatally to e-cig aerosols with nicotine and in males exposed to e-cig aerosols compared with control animals exposed to air. MMP9 (matrix metalloproteinase 9), a downstream target of PAI-1, was downregulated in both sexes exposed to e-cig aerosols with nicotine. No differences in lung histology were observed among any of the treatment groups. Overall, adult mice exposed prenatally to e-cig aerosols could be predisposed to developing pulmonary disease later in life. Thus, these findings suggest that vaping during pregnancy is unsafe and increases the propensity for later-life interstitial lung diseases.

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Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to Electronic-Cigarette Aerosols Leads to Sex-Dependent Pulmonary Extracellular-Matrix Remodeling and Myogenesis in Offspring Mice

Wang

Sundar

Blum

et al. 2020

Am J Respir Cell Mol Biol

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“…The development of synthetic PAI-1 inhibitors has focused on their potential utility as antithrombotic agents or as a treatment option for acute and chronic fibrotic disease (Brown 2010). Over the last 20 years, several low molecular weight PAI-1 antagonists have been developed and tested in vitro, in animal models in vivo, and in clinical trials (Brown 2010;Simone et al 2014). Indeed, the available data suggest that inhibitory approaches directed to PAI-1 SERPIN activity may well be a promising therapeutic strategy to limit vascular fibrosis, reduce tumor aggressiveness, reduce airway remodeling in a model of chronic asthma, and promote regenerative tissue repair.…”

Section: Discussionmentioning

confidence: 99%

S100a6

Donato¹,

Sorci²,

Giambanco³

2018

Encyclopedia of Signaling Molecules

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“…A highly-interactive plasmin-matrix metalloproteinase (MMP) pericellular proteolytic cascade is finely “titrated” both temporally and spatially by SERPINE1 (PAI-1). This complex cooperating system of proteases and inhibitors is fundamental to normal tissue repair and development of chronic diseases (adapted from [ 11 ]).…”

Section: Figurementioning

confidence: 99%

Balancing AhR-Dependent Pro-Oxidant and Nrf2-Responsive Anti-Oxidant Pathways in Age-Related Retinopathy: Is SERPINE1 Expression a Therapeutic Target in Disease Onset and Progression?

Higgins

2015

J Mol Genet Med

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Chemical Antagonists of Plasminogen Activator Inhibitor-1: Mechanisms of Action and Therapeutic Potential in Vascular Disease

Cited by 12 publications

References 97 publications

Prenatal Exposure to Electronic-Cigarette Aerosols Leads to Sex-Dependent Pulmonary Extracellular-Matrix Remodeling and Myogenesis in Offspring Mice

Prenatal Exposure to Electronic-Cigarette Aerosols Leads to Sex-Dependent Pulmonary Extracellular-Matrix Remodeling and Myogenesis in Offspring Mice

S100a6

Balancing AhR-Dependent Pro-Oxidant and Nrf2-Responsive Anti-Oxidant Pathways in Age-Related Retinopathy: Is SERPINE1 Expression a Therapeutic Target in Disease Onset and Progression?

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